A murine model of long-term colonization with Candida albicans, established by intubating infant CBA/J mice, was used to study the effects of colonization on the development of Candida-specific immune responses in mature animals. Two striking consequences were stimulation of protective immune responses, as evidenced by increased survival and decreased numbers of colony-forming units in mice challenged intravenously (iv), and priming of the T cell component responsible for delayed hypersensitivity (DH). Colonized mice, tested as adults by using a cell wall-derived antigen, had little or no demonstrable DH. If inoculated once cutaneously with viable Candida, however, they responded with significantly enhanced DH reactions that could not be correlated with the cutaneous inoculation. Inoculation of the same number of dead organisms into infant mice neither primed animals for enhanced DH nor stimulated protective immunity. Antibody to cytoplasmic antigens of Candida was demonstrable in colonized animals, and its production was increased significantly in animals challenged iv with the highest dose of blastoconidia.